ERβ exerts multiple stimulative effects on human breast carcinoma cells

Hou, Yi; Yuan, Sheng; Li, He Cheng; Wu, Jiong; Lu, Jin Song; Liu, Gang; Lu, Li; Shen, Zhen; Ding, Jian; Shao, Zhi Ming

doi:10.1038/sj.onc.1207765

Cited by 66 publications

(55 citation statements)

References 28 publications

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“…40 In addition, in vivo and in vitro studies have demonstrated that ERb exerts stimulative effects on breast cancer development and metastasis. 41 It has also been shown that ERb negatively affects malignant cell tumorigenesis. 19,42,43 Although to our knowledge the exact correlation between ERb expression and tumor progression in thymic epithelial tumors is still unclear, ERb is suggested as a potential target in the treatment of ERb-positive thymomas and thymic carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Steroid receptor expression in thymomas and thymic carcinomas

Mimae

Tsuta

Takahashi

et al. 2011

Cancer

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BACKGROUND: Although protein expressions of glucocorticoid receptor (GR), estrogen receptors (ERa and ERb), progesterone receptor A (PgR-A), and androgen receptor (AR) were shown to play roles in the growth and differentiation of normal thymus and thymic tumors, to the authors' knowledge their association with patient characteristics and prognosis has yet to be determined. METHODS: A series of 140 thymic epithelial tumors (57 type A þ AB thymomas, 40 type B1 þ B2 thymomas, 6 type B3 thymomas, and 37 thymic carcinomas) were examined for GR, ERa, ERb, PgR-A, and AR expression using immunohistochemistry. In addition, the correlation between expression of these hormone receptors and clinicopathologic factors and overall survival (OS) was assessed. RESULTS: GR and ERb demonstrated a high rate of expression in thymomas and thymic carcinomas (82.9% and 76.4%, respectively), whereas rates of ERa, PgR-A, and AR expression were low (13.6%, 0.71%, and 23.6%, respectively). A significant correlation (P < .05) was found between ERa expression and tumor size and between ERb expression and tumor stage. Multivariate analyses revealed that histologic subtype (P ¼ .0039), tumor stage (P ¼ .0012), and GR expression (P ¼ .0025) were significantly correlated with the 10-year OS rate. CONCLUSIONS: GR and ERb demonstrated high rates of expression in thymomas and thymic carcinomas. Furthermore, multivariate analysis revealed that GR expression was associated with better prognosis in patients with surgically resected thymomas and thymic carcinomas. Cancer 2011;117:4396-

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Section: Discussionmentioning

confidence: 99%

Steroid receptor expression in thymomas and thymic carcinomas

Mimae

Tsuta

Takahashi

et al. 2011

Cancer

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“…Most cell line models in which ERb1 has been stably expressed either inducibly or constitutively show that overexpression of ERb1 inhibits proliferation irrespective of whether it is coexpressed with ERa (Paruthiyil et al, 2004;Strom et al, 2004;Murphy et al, 2005) or not (Lazennec et al, 2001;Cheng et al, 2004). However, two studies using cell line models have been published in which stable constitutive overexpression of ERb1 resulted in increased proliferation (Tonetti et al, 2003;Hou et al, 2004) although in the former publication the short form of ERb1 (truncated by 45 amino acids from the N-terminus) was used. Both breast cancer cell lines used (MDA-MB-231 and MDA-MB-435) are typically ERa negative and therefore can be considered to represent the ERb alone expressing breast tumours cohort in vivo.…”

Section: Discussionmentioning

confidence: 99%

Expression of oestrogen receptor-β in oestrogen receptor-α negative human breast tumours

et al. 2006

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To analyse the phenotype of breast tumours that express oestrogen receptor-b (ERb) alone tissue microarrays were used to investigate if ERb isoforms are associated with specific prognostic markers and gene expression phenotypes in ERa-negative tumours. ERa-negative tumours were positive for ERb1 in 58% of cases (n ¼ 122/210), total ERb in 60% (n ¼ 115/192) and ERb2/cx in 57% of cases (n ¼ 114/199). Oestrogen receptor-b1 and total ERb were significantly correlated with Ki67 (r ¼ 0.28, Po0.0001, n ¼ 209; r ¼ 0.29, Po0.0001, n ¼ 191) and with CK5/6, a marker of the basal phenotype (r ¼ 0.20, P ¼ 0.0106, n ¼ 170; r ¼ 0.18, P ¼ 0.0223, n ¼ 158). ERb2/cx was strongly associated with p-c-Jun and NF-kBp65 (r ¼ 0.53, Po0.0001, n ¼ 93; r ¼ 0.35, Po0.0001, n ¼ 176). This study shows that a range of ERb isoform expression occurs in ERa-negative breast tumours. While expression of ERb1, total and ERb2/cx are correlated, individual forms show associations with certain phenotypes that suggest different roles in subsets of ERanegative cancers. Based on our in vivo observations, ERb may have the potential to become a therapeutic target in the specific subcohort of ERa-negative breast cancers.

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“…Introduction of ERβ into ER-MDA-MB-435 and MDA-MB-231 breast cancer cells increases cell proliferation in an E2-independent manner, cell invasiveness, and metastasis [73]. In contrast, introduction of ERα into ER-breast cancer cells generally decreases their proliferation in an E2-dependent manner, and their invasiveness and migration by both ligand-dependent and ligand-independent mechanisms [74,75].…”

Section: Potential Role Of Erα/erβ Heterodimers In Biological Responsmentioning

confidence: 98%

ERβ in breast cancer—Onlooker, passive player, or active protector?

2008

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The role of estrogen exposure in breast cancer risk is well-documented, and both estrogen synthesis and actions through the estrogen receptor (ER) have been targeted by therapies to control hormonedependent breast cancer. The discovery of a second ER form and its therapeutic implications sparked great interest. Both the original ERα and the more recently identified ERβ subtypes bind and respond similarly to many physiological and pharmacological ligands. However, differences in phytoestrogen binding have been noted, and subtype-specific ligands have been developed. Cell-based assays show that ERβ and its variants are generally less active on gene transcription than ERα, and may influence ERα activity; however, both gene-and cell-specific responses occur, and nongenomic activities are less well explored. Specific ligands, and methods to disrupt or eliminate receptor subtype expression in animal and cell models, demonstrate that the ERs have both overlapping and distinct biological functions. Overall, in cell-based studies, ERα appears to play a predominant role in cell proliferation, and ERβ is suggested to be antiproliferative.The potential for distinct populations of breast tumors to be identified based on ER subtype expression, and to exhibit distinct clinical behaviors, is of greatest interest. Several studies suggest that the majority of ER-positive tumors contain both subtypes, but that some tumors contain only ERβ and may have distinct clinical behaviors and responses. Expression of ERβ together with ERα favors positive responses to endocrine therapy in most studies, and additional studies to determine if the addition of ERβ to ERα as a tumor marker is of clinical benefit are warranted. In contrast, the positive association between ERβ and HER2 expression in high-grade ERα-negative breast cancer does not favor positive responses to endocrine therapy. Expression of ERβ in specific clinical subpopulations, and the potential for therapies targeting ERβ specifically, is discussed.

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ERβ exerts multiple stimulative effects on human breast carcinoma cells

Cited by 66 publications

References 28 publications

Steroid receptor expression in thymomas and thymic carcinomas

Steroid receptor expression in thymomas and thymic carcinomas

Expression of oestrogen receptor-β in oestrogen receptor-α negative human breast tumours

ERβ in breast cancer—Onlooker, passive player, or active protector?

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